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dc.contributor.authorJamin, Y
dc.contributor.authorSmyth, L
dc.contributor.authorRobinson, SP
dc.contributor.authorPoon, ESC
dc.contributor.authorEykyn, TR
dc.contributor.authorSpringer, CJ
dc.contributor.authorLeach, MO
dc.contributor.authorPayne, GS
dc.date.accessioned2018-06-26T10:44:53Z
dc.date.issued2011-05
dc.identifier.citationNMR in biomedicine, 2011, 24 (4), pp. 343 - 350
dc.identifier.issn0952-3480
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1935
dc.identifier.eissn1099-1492
dc.identifier.doi10.1002/nbm.1597
dc.description.abstractThe pseudomonad protein, carboxypeptidase G2 (CPG2), is a prodrug-activating enzyme utilized in the targeted chemotherapy strategies of antibody- and gene-directed enzyme prodrug therapy (ADEPT and GDEPT). We have developed a noninvasive imaging approach to monitor CPG2 activity in vivo that will facilitate the preclinical and clinical development of CPG2-based ADEPT and GDEPT strategies. Cleavage of the novel reporter probe, 3,5-difluorobenzoyl-L-glutamic acid (3,5-DFBGlu), by CPG2, in human colon adenocarcinoma WiDr xenografts engineered to stably express CPG2, was monitored using (19)F MRSI. The high signal-to-noise ratio afforded by the two MR-equivalent (19)F nuclei of 3,5-DFBGlu, and the 1.4 ppm (19)F chemical shift difference on CPG2-mediated cleavage, enabled the dynamics and quantification of the apparent pharmacokinetics of 3,5-DFBGlu and its CPG2-mediated cleavage in the tumor to be evaluated. In addition, the apparent rate of increase of 3,5-difluorobenzoic acid concentration could also provide a biomarker of CPG2 activity levels in tumors of patients undergoing CPG2-based therapies, as well as a biomarker of treatment response. The addition of in vivo reporter probes, such as 3,5-DFBGlu, to the armamentarium of prodrugs cleaved by CPG2 affords new applications for CPG2 as a gene reporter of transgene expression.
dc.formatPrint-Electronic
dc.format.extent343 - 350
dc.languageeng
dc.language.isoeng
dc.subjectCell Line, Tumor
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectFluorine
dc.subjectBenzoic Acid
dc.subjectgamma-Glutamyl Hydrolase
dc.subjectGlutamic Acid
dc.subjectXenograft Model Antitumor Assays
dc.subjectFemale
dc.titleNoninvasive detection of carboxypeptidase G2 activity in vivo.
dc.typeJournal Article
dcterms.dateAccepted2010-06-22
rioxxterms.versionofrecord10.1002/nbm.1597
rioxxterms.licenseref.startdate2011-05
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNMR in biomedicine
pubs.issue4
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Gene & Oncogene Targeting
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Gene & Oncogene Targeting
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.publication-statusPublished
pubs.volume24
pubs.embargo.termsNot known
icr.researchteamGene & Oncogene Targetingen_US
icr.researchteamPaediatric Solid Tumour Biology and Therapeuticsen_US
icr.researchteamMagnetic Resonanceen_US
icr.researchteamPre-Clinical MRIen_US
dc.contributor.icrauthorPayne, Geoffreyen
dc.contributor.icrauthorSmyth, Lynette Anneen
dc.contributor.icrauthorLeach, Martinen
dc.contributor.icrauthorSpringer, Carolineen
dc.contributor.icrauthorRobinson, Simonen
dc.contributor.icrauthorJamin, Yannen
dc.contributor.icrauthorPoon, Evonen


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